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Modulation of the biological function of a synthetic carbohydrate antigen related to Streptococcus pneumoniae infections
No full textImmunology of carbohydrate antigens related to Streptococcus pneumoniae infection : synthesis of a glycolipid construct
No full textCarbohydrates in the form of capsular polysaccharides are the major components on the surface of bacteria, and are important virulence factors of invading bacteria. Immunity against these components confers protection against the infectious disease. However, there are several problems associated to the development of vaccines based on saccharidic antigens. Bacterial polysaccharides are poorly immunogenic T-independent antigens, and they are able to induce only the release of low affinity antibody from B lymphocytes, but not their differentiation.1 The T-lymphocyte independent nature of a polysaccharide may be overcome by conjugating the native or depolymerized polysaccharide to a carrier protein. In a similar way, the conjugation to an immunoadjuvant could lead to a construct able to stimulate a sustainable antibody response. Recently, lipoproteins, i.e. Pam3Cys, have been shown as potent activators of B-lymphocytes and macrophages,2 and thus represent a promising tool for the development of conjugated vaccines.
Herein, the synthesis of a glycoconjugate where the repeating unit of Streptococcus pneumoniae (SP) type 19F capsular polysaccharide is linked to a Pam3CysSer residue through an amino propyl linker will be presented as a case study. The final aim is to evaluate the influence of the lipopeptide on the immune response towards SP, and if antigen specific antibodies can be elicited with low molecular weight conjugates of Pam3CysSer with a saccharide-based hapte
Synthesis of fragments of Salmonella Typhi capsular polysaccharide and their zwitterionic analogues
No full textSalmonella enterica serovar Typhi (often called S. Typhi) is a motile Gram-negative bacterium, whose capsular polysaccharide (often referred to as Vi antigen) is an anionic polymer composed of α-(1-4)-linked N-acetyl-galactosaminuronic acid repeating units predominantly O-acetylated at position 3. The degree of acetylation was found to be crucial for the immunogenicity. We investigated two different synthetic routes for the oligomers assembly: a late stage post-glycosylation oxidation approach and a pre-glycosylation oxidation strategy, the latter employing suitably protected uronates donor and acceptor. Glycosylation reactions were carried out using N-phenyltrifluoroacetimidates as glycosyl donors, and experimental conditions were carefully screened in order to ensure the stereoselective formation of the desired α product. The azido group at C-2 can be converted into either an acetamido function (natural Vi) or a free amino group (zwitterionic derivatives). Finally, a pentenyl linker was installed at C-1 of the reducing end in order to facilitate the subsequent conjugation to protein carrier and/or multivalent scaffolds
Synthesis of fragments of Salmonella Typhi capsular polysaccharide and their zwitterionic analogues
No full textWe will report on the synthesis of oligomers of Salmonella enterica serovar Typhi (often called S. Typhi) CPS, and their zwitterionic analogues. S. Typhi is a motile Gram-negative bacterium, whose CPS (often referred to as Vi antigen) is an anionic polymer composed by α-(1-4)-linked N-acetyl galactosaminuronic acid repeating units predominantly O-acetylated at position 3. We developed a strategy based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approaches using disaccharide donors. All these intermediates were obtained from commercially available D-galactosamine hydrochloride. The non participating azide group was used to mask C-2 amino functionality, which can be converted into the animo group (ZPS) or into the acetamido function (natural Vi) and allows the formation of 1,2-cis glycosidic linkages. Glycosylation reactions were carried out using N-phenyltrifluoroacetimidates as glycosyl donors, yielding
stereoselectively the desired α product. C-6 oxidation was done with TEMPO/NaClO2. By orthogonally protecting
position 3 we were able to obtain both fully 3-O-acetylated and fully 3-O-deactetylated oligomers. Finally, a suitable l
inker was installed at C-1 of the reducing end in order to facilitate a subsequent conjugation to protein carrier and/or
multivalents caffolds. The immunological properties of the synthetic oligomers will be also investigated in order to correlate the structural features (in particular 3-O-acetylation) with their biological behaviour
Synthesis of fragments of salmonella typhi capsular polysaccharide
No full textWe will report on the synthesis of oligomers of Salmonella enterica serovar Typhi (often called S. Typhi) capsular polysaccharide (CPS). S. Typhi is a motile Gram-negative bacterium, whose CPS (often referred to as Vi antigen) is an anionic polymer composed of α-(1-4)-linked N-acetyl galactosaminuronic acid repeating units predominantly O-acetylated at position 3. We developed a strategy based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approach using disaccharide donors. All these intermediates were obtained from commercially available D-galactosamine hydrochloride. Glycosylation reactions were carried out using N-phenyl-trifluoroacetimidates as glycosyl donors, yielding stereoselectively the desired α product. Late stage C-6 oxidation was done by a Dess-Martin/Pinnick oxidation. Finally, a suitable linker was installed at C-1 of the reducing end in order to facilitate the subsequent conjugation to protein carrier and/or multivalent scaffolds
Synthesis and biological evaluation of a trisaccharide repeating unit derivative of streptococcus pneumoniae 19A capsular polysaccharide
No full textStreptococcus pneumoniae (SP) is a common human pathogen associated with a broad spectrum of disease and it is still a leading cause of mortality and morbidity worldwide [1]. Nowadays the most effective strategy to reduce the burden of disease caused by SP is vaccination. Administered vaccines contain fragments of bacterial capsular polysaccharide (CP), which are important surface antigens of these invading bacteria. New research strategies in this field aim at developing nanomaterials loaded with carbohydrate antigens, which are emerging as synthetic vaccine candidates [2,3]. The prerequisite of this approach is the identification of the shortest polysaccharide fragment able to be recognized by the natural antibody and to be immunogenic. In this framework has emerged our interest in SP 19A serotype, which is one of the serotype responsible for the bulk of pneumococcal disease [4]. In particular, we aim at developing a derivative of the SP19A repeating unit, -D-ManpNAc-(14)--D-Glcp-(13)-Rhap-(1-O-phosphate), still endowed with biological activity and suitable for conjugation to different nanomaterials.
Herein we will describe the synthesis of compound 1, the saccharide portion of SP 19A repeating unit conjugated at the reducing end to an aminopropyl linker. This compound has been obtained through a glycosylation reaction between a properly protected thiophenyl -D-ManpNAc-(14)--D-Glcp disaccharide and a new suitable -amino propyl rhamnoside acceptor.
Classical competitive Elisa assay demonstrated that compound 1 has inhibitory properties and is recognized by the anti-19A antibody
Synthesis of fragments of Salmonella Typhi capsular polysaccharide and their zwitterionic analogues
No full textWe will report on the synthesis of oligomers of Salmonella enterica serovar Typhi (often called S. Typhi) CPS, and their zwitterionic analogues. S. Typhi is a motile Gram-negative bacterium, whose CPS (often referred to as Vi antigen) is an anionic polymer composed by α-(1-4)-linked N-acetyl galactosaminuronic acid repeating units predominantly O-acetylated at position 3. We developed a strategy based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approaches using disaccharide donors. All these intermediates were obtained from commercially available D-galactosamine hydrochloride. The non participating azide group was used to mask C-2 amino functionality, which can be converted into the animo group (ZPS) or into the acetamido function (natural Vi) and allows the formation of 1,2-cis glycosidic linkages. Glycosylation reactions were carried out using N-phenyltrifluoroacetimidates as glycosyl donors, yielding
stereoselectively the desired α product. C-6 oxidation was done with TEMPO/NaClO2. By orthogonally protecting
position 3 we were able to obtain both fully 3-O-acetylated and fully 3-O-deactetylated oligomers. Finally, a suitable l
inker was installed at C-1 of the reducing end in order to facilitate a subsequent conjugation to protein carrier and/or
multivalents caffolds. The immunological properties of the synthetic oligomers will be also investigated in order to correlate the structural features (in particular 3-O-acetylation) with their biological behaviour
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Glycocalixarenes decorated with Streptococcus pneumoniae 19F capsular polysaccharide fragments bind to anti-19F antibodies
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